Effects of Tenapanor on Cytochrome P450-Mediated Drug-Drug Interactions.

ABSTRACT: Tenapanor (RDX5791, AZD1722) is an inhibitor of sodium/hydrogen exchanger isoform 3 in development for the treatment of constipation-predominant irritable bowel syndrome and the treatment of hyperphosphatemia in patients with chronic kidney disease on dialysis. We aimed to investigate whether tenapanor inhibits or induces cytochrome P450s (CYPs). In vitro experiments assessing the potential of tenapanor to affect various CYPs indicated that it could inhibit CYP3A4/5 (IC₅₀ 0.4-0.7 μM). An open-label, phase 1 clinical study (NCT02140268) evaluated the pharmacokinetics of the CYP3A4 substrate midazolam when administered with and without tenapanor. Healthy volunteers received a single oral dose of midazolam 7.5 mg on day 1 followed by tenapanor 15 mg twice daily on days 2 to 15, wit

SUBMITTER: Johansson S 

PROVIDER: S-EPMC5599994 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature